The possibility is there. As you say, humans are quote "advanced", though I would use the word more "complex" (or maybe that we just don't have full comprehension . . . yet), and that means that there are more processes to repress to get back to stem cell/progenitor/dedifferentiated status. But if the dna "blueprints" are still there, we should be able to create an environment (albeit complex) to facilitate regeneration.The cytokine and hormone environment has been brought up in the literature to be conducive to fibrosis. I believe that it is cytokines, though a different cytokine environment than what is expressed now, may be beneficial towards regeneration. True, we may have to repress the immune system thru out the regeneration process though.Now the hormone may be the key. Why else would innervation be a requirement for regeneration? A hormone that starts the differentiation development again. And has to start the regeneration process with gradients of factors right at the beginning. With all that massive destruction of cells (amputation), there has to be a release of a threshold gradient of some factor, or possibly factors. This release should trigger the release of this hormone in the nerve axon? A type of neurotransmitter? That is released upon the threshold gradient of massive destruction. Cytokines of course would be involved as they react to the destruction also. But which ones?

The word cancer is used to describe a general heading of cells gone wild. Somehow they can not carry on their specific function, and may find alternative ways of producing new functions. This can have evolutionary implications. Now some are not viable to the organism, and sometimes they are viable. Procreation of these new functions will produce evolution. Survival of the fitness (though with modern medicine, any viable functioning organism seems to procreate ) is the theme. Regeneration may be one of those functions. . . . one day (which yes could mean a thousand years or so in the eyes of evolution).

I think I got your point, and yes, "complex" is a good word to describe the same I tried with "advanced". Anyways, I'm not too sure there's much evolutionary pressure towards regeneration in humans, quite the contrary: we can probably make excellent artificial limbs long before evolution has time to do anything about it :)

This is not to say it is impossible to make humans regenerate a limb, but I fear it's next to it. I think it's easier and more realistic to design artificial limbs and organs, maybe even partly/fully biological ones. But you never know, maybe after a few centuries you get to tell me "I told you so!" :P

The more we tinker around with stem cells, the closer we will get to unlocking the mysteries. I am not a big fan of letting Mother Nature do all the tinkering around: evolutionary pressure. Though she gets to make the big evolutionary ones because she can do what she wants and has no rules to follow. Humans on the other hand . . . .

kolean, i would like you to be right, but i fear that the more we look at in vivo dedifferentiation followed by differentiation into another cell type we see that it might not be a viable treatment option. right now it seems to me that transdifferentiation might be a more viable approach to explore..

"As a biologist, I firmly believe that when you're dead, you're dead. Except for what you live behind in history. That's the only afterlife" - J. Craig Venter

Can you clarify the distinction between "transdifferentiation" and the "dedifferentiation and then differentiation" that occurs during epimorphic regeneration? Is it just the process of reployment of developmental programming during the latter, while the former has a different process of reprogramming? Because basically, are they not both repressing the phenotypic expression of one cell and transforming it into the phenotypic expression of another cell?

with transdifferentiation, you are not passing through the stem cell state, you're just turning one cell type into another more or less directly. this is good because it by-passes the tricky stem cell state. here's a nice straightforward paper where this approach is used:http://www.nature.com/nature/journal/v4 ... 07314.html

"As a biologist, I firmly believe that when you're dead, you're dead. Except for what you live behind in history. That's the only afterlife" - J. Craig Venter

I don't have full access to the article right now, so what does it mean by: . . . using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells.

well it's like iPS cells: they very very closely resemble embryonic stem cells, but they're not exactly identical. Just like that, those cells don't have all the same characteristics of beta cells (if i remember correctly they don't cluster into islands).

"As a biologist, I firmly believe that when you're dead, you're dead. Except for what you live behind in history. That's the only afterlife" - J. Craig Venter

ok dont take this as scietific fact as it is just a theory of mine but i believe it is very possable as we are able to regenerate cells as babies and as we are just a fetus but we loose the ability to coordinate our cells. it is the ability to coordinate there cells and cell memory that allows some creatures to regenerate and i believe that our liver is the key to unlocking man kinds full potential. your quetion should be is it possable to use stem cells to engineer a human liver but during its growth process to introduce hormones from a salamander or axolotl to mutate the DNA enough to create human cell with the ability of cell memory and coordination or if it is possable to locate the exact pair genes that give salamanders and axolotl's the abilty to do this already and introduce that to human but i honestly dont really know what im talking about but someone proove my theory is absolutely impossable and i'll shake ya hand.

Probably because a human liver can regenerate itself (unless less than 25% of its mass).

You are thinking like an organ system biologist when you think that the liver can show us how to regenerate. Now with the liver, it just regenerates the same cell over and over (hepatocytes) with the blood vessels and other vessels (epithelium/endothelial) spreading thru it, to produce the tissue mass.

Now regeneration in a salamander can be plain like the lens regeneration, or it could be as complex as the whole tail or arm/leg. I do not think hormones mutate genes/DNA to create cellular memory. Plus you can not mutate or mess with the DNA genome as that is your original blueprint.

I think that they just re-express developmental genes (basic original blueprint that has been repressed after the embryological process was completed) using blastemal cells (pluripotent or totipotent seems to be the question lately - but albeit a type of stem cell).

Blastemal cells are regular cells that de-differentiated from the wound site (though not all the way back to beginning stem cells, as a new article remarks on cellular memory for muscle and nerve cells mostly) and grow to the right size of mass needed for the regenerating appendage. Then they begin to differentiate back to their programmed cell fate.

Personally, I think that miRNA and PcG/chromatin remodeling will be what we find that lets us dedifferentiate the cell's programmed fate, and then redifferentiate it with the appropriate environment (here is where the hormones, cytokines, transcription factors, etc. come into play).